Opportunities and considerations for studying liver disease with microphysiological systems on a chip.

Advances in microsystem engineering have enabled the development of highly controlled models of the liver that better recapitulate the unique in vivo biological conditions. In just a few short years, substantial progress has been made in creating complex mono- and multi-cellular models that mimic key metabolic, structural, and oxygen gradients crucial for liver function. Here we review: 1) the state-of-the-art in liver-centric microphysiological systems and 2) the array of liver diseases and pressing biological and therapeutic challenges which could be investigated with these systems. The engineering community has unique opportunities to innovate with new liver-on-a-chip devices and partner with biomedical researchers to usher in a new era of understanding of the molecular and cellular contributors to liver diseases and identify and test rational therapeutic modalities.